Plasma proteomics analysis of vitamin C supplementation in people with type 2 diabetes

Background Evidence from randomised controlled trials shows that vitamin C (VC) supplementation may improve cardiometabolic health outcomes in people with type 2 diabetes (T2D). Plasma proteomics following VC supplementation may help to further enhance our understanding of VC’s therapeutic effects and biological mechanisms in T2D. Therefore, our aim was to explore the effects of VC supplementation on the plasma proteome in people with T2D. Methods A double-blind, placebo-controlled, cross-over trial was undertaken in people with T2D, who were administered 1000 mg/day VC or placebo for 4 months. Plasma proteins in 26 participants (22 male, 4 female, age 62.6 ± 6.5 years, HbA1c 60 ± 11 mmol/mol [7.6 ± 0.7%]) were quantified by liquid chromatography/mass spectrometry with data independent acquisition. Differential protein expression was assessed for VC post-supplementation vs. control [pooling of all non-active conditions Results Across imputed and non-imputed analyses, ten proteins were significantly downregulated and one upregulated following VC supplementation (> 1.5-fold change; q < 0.05). The largest magnitude changes observed (> 2-fold) were decreases in Alpha-amylase 1 (AMY1), Serum amyloid protein A1 (SAA1), Serum amyloid protein A2 (SAA2), and Lysine demethylase-5B (KDM5B); while AMY1, Myosin-1 (MYH1), and Translation initiation factor eIF2B subunit beta (EIF2B) were significantly decreased in all analyses. Gene Ontology pathway enrichment revealed underrepresentation of acute-phase response proteins following VC supplementation. SAA1 and C-reactive protein correlated with previously reported improved glycaemic-related measures with VC supplementation. Conclusions VC supplementation significantly decreased several proteins in plasma, with functions relating to the acute-phase response of the immune system, dietary carbohydrate digestion, and skeletal muscle contraction. Alterations in acute-phase proteins are implicated in improved glycaemic outcomes in people with T2D with VC supplementation. Novel biomarkers of VC effects identified in people with T2D included AMY1, EI2BB, MYH1, KDM5B, Ectonucleotide pyrophosphatase/phosphodiesterase family member-2, and Biliverdin reductase-B.